Project Summary: Cognitive decline and dementia after stroke is a major public health problem, with risk of dementia more than doubling after stroke and affecting more the 2 million people in the United States alone. Yet, there are no effective treatments to prevent cognitive decline and dementia after stroke. Silent brain infarction has been associated with cognitive decline, especially among those at high risk for cardio-embolism. It is therefore likely that treatments that reduce the incidence of silent infarcts in stroke patients at high risk for cardio-embolism, will also reduce the rate of cognitive decline and dementia. To test this, we propose to conduct an ancillary study to the NINDS-sponsored ARCADIA trial. ARCADIA compares treatment with apixaban versus aspirin to prevent a recurrent clinical stroke in patients with cryptogenic stroke and left atrial cardiopathy. We are taking advantage of the parent trial to address the possibility that apixaban might also reduce the incidence of silent infarction and be associated with better cognitive function over time compared to aspirin. We will enroll 500 patients from the 1,100 that will participate in ARCADIA. Patients who participate in the ancillary study (ARCADIA-CSI) will receive cognitive assessments at baseline and yearly thereafter using a telephone-based cognitive battery. We will test the hypothesis that the slope of change in cognitive function is less steep in patients on apixaban compared to patients on aspirin therapy. We will also collect an initial MRI around the time of the qualifying stroke and a follow-up MRI at the time that the subject completes participation in the ARCADIA parent study. Based on these two MRI scans we will assess the incidence of new silent infarcts during the follow-up period and test the hypothesis that apixaban treatment results in a reduction of the percentage of patients with silent infarcts compared to aspirin therapy. An explorative analysis will also look for the relationship between new silent infarcts and cognitive change. Our project will be among the first to determine prospectively the impact of silent infarction on cognitive function. And, if cognitive decline can be ameliorated by apixaban, then we will have established the first ever treatment for the prevention of post-stroke cognitive decline.